Most current functional magnetic resonance imaging (fMRI) techniques measure the change in water T2* or T2 caused by blood oxygenation-level dependent (BOLD) contrast, which are based on the hemodynamic responses to neuronal activity. However, the coupling between neuronal activity and hemodynamics is complex, and the spatial and temporal resolutions of hemodynamic-based fMRI are intrinsically limited by properties of the vasculature. In order to improve the spatial specificity and to obtain a faster temporal response, the imaging signal should directly originate from tissue (i.e., neuronal cells), rather than from blood vessels. In this project, a novel fMRI technique based on tissue T1rho will be developed, and its spatial and temporal characteristics will be examined. T1rho is the spin-lattice relaxation time in the rotating frame during an applied spin-locking pulse, and has been found to be sensitive to intracellular pH level as well as macromolecular composition and density. This tissue T1rho fMRI contrast is presumably induced by an acidification of neuronal cells during activation, and is expected to be faster, with spatial origins more specific to sites of neural activity than hemodynamic-based fMRI. Thus, tissue T1rho fMRI contrast may greatly improve the accuracy of noninvasive functional brain mapping in basic and clinical neuroscience research. PUBLIC HEALTH RELEVANCE: This investigation aims to develop a novel non-invasive brain imaging technique that can be faster and more accurate than conventional techniques.